Aprepitant of Formula I is a substance P/neurokinin 1 (NK1) receptor antagonist, chemically described as 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one and in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.

The key intermediate (2R,3S)-4-benzyl-3-(4-fluorophenyl)morpholin-2-yl 3,5-bis(trifluoromethyl)benzoate of Formula II, is useful in the preparation of pharmaceutical compounds, which are substances P (or neuroklinin-1) receptor antagonists.

U.S. Pat. No. 5,719,147 provides a process for the preparation of compound of Formula II, which involves reacting (3S)-4-benzyl-3-(4-fluorophenyl)morpholin-2-one, the compound of Formula III,
with L-selectride, and treating the reaction mixture with 3,5-bis(trifluoromethyl) benzoyl chloride, the compound of Formula IV,
isolating the crude product using flash chromatography on silica gel using hexane/ether.
U.S. Pat. Nos. 6,096,742 and 6,229,010 provide a process for the preparation of compound of Formula II, wherein the process involves isolating the product as a hydrochloride salt by treating with hydrochloric acid in diethyl ether, which is then converted into freebase by reacting it with toluene and aqueous sodium bicarbonate.
J. Med. Chem., 1998, 41, 4607-4614, provides a process for the preparation of compound of Formula II wherein the process involves isolating the crude product using flash chromatography on silica gel and then crystallizing from isopropyl alcohol.
Another key intermediate of Formula VII is also useful in the preparation of pharmaceutical compounds, which are substances P (or neuroklinin-1) receptor antagonists.

U.S. Pat. Nos. 5,719,147 and 5,637,699 provides a process for the preparation of compound of Formula I, which involves dissolving the compound of formula VII in xylene and heating to 137° C. to obtain aprepitant.
U.S. Pat. Nos. 6,096,742 and 6,229,010 provides a process for the preparation of compound of Formula I, which involves dissolving the compound of formula VII in xylene and disopropylethylamine and heating to 135° C. to obtain aprepitant.
PCT Application No. WO 03/089429 provide a process for the preparation of compound of Formula I, which involves partially concentrating the organic layer containing the compound of formula VII and toluene at atmospheric pressure, heating the resulting solution in toluene to 140-150° C. to obtain aprepitant.